Lung cancer is the most common cancer and the leading cause of cancer-related deaths worldwide. NSCLC constitutes between 80-85% of all lung cancers and more than 30% of those are diagnosed with stage III disease over the age of 65. Despite this large population, elderly patients are often excluded or underrepresented in clinical trials resulting in limited treatment options for this population of patients. Given that NSCLC is a heterogenous disease requiring a multidisciplinary treatment approach, and the limited treatment data available in this population, the optimal treatment strategy for stage III NSCLC in the elderly needs to be further explored.

A group of investigators at The Ohio State University in the United States conducted a retrospective study to compare the effectiveness of RT alone verses CRT in elderly patients ≥70 years old with stage III NSCLC not treated surgically. Patients ≥70 years old with stage III NSCLC not surgically treated from 2003-2014 were selected from the National Cancer Database. Patients were divided into two cohorts: patients treated with definitive RT and patients treated with definitive CRT. The CRT patients were considered to have received concurrent CRT if chemotherapy was delivered within 30 days prior to or after initiation of RT, while sequential CRT was defined as RT delivered ˃30 days after initiation of chemotherapy. The OS between treatment groups was compared using the Kaplan-Meier method and Cox proportional hazards regression before and after propensity score matching (PSM) to reduce potential selection bias.

The results of the study were published in the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer (IASLC). The study identified 5,023 elderly patients treated with definitive RT and 18,206 patients treated with CRT. Univariate analysis revealed that younger age, male sex, white race, higher income, stage IIIB, increased distance from the treating hospital and a Charlson-Deyo score <1 were associated with higher odds of receiving CRT. These covariates were used to calculate propensity scores. Treatment with CRT was associated with improved OS compared to RT before PSM (HR=0.66, 95%CI 0.64-0.68, p<0.0001) and after PSM (HR=0.91, 95%CI 0.85-0.96, p=0.002). After PSM, treatment with CRT corresponded to a 33% reduction in the risk of death (HR=0.67, 95%CI 0.64-0.70, p<0.001). The benefit of CRT was greater for elderly patients treated with multi-agent chemotherapy (HR=0.64, 95%CI 0.61-0.67, p<0.001) compared with single-agent chemotherapy (HR=0.83, 95%CI 0.75-0.92, p<0.001). Finally, patients treated with CRT were further subdivided into those treated with concurrent verses sequential CRT with 15,840 treated with concurrent CRT and 2,366 treated with sequential CRT. Treatment with sequential CRT corresponded to a 9% reduction in the risk of death (HR=0.91, 95%CI 0.85-0.96, p=0.002).

The authors comment that, “Treatment of the elderly with locally advanced NSCLC is challenging and, with an aging population, will remain an issue for the U.S. healthcare system for the foreseeable future. To our knowledge, our study represents the largest reported cohort of elderly stage III NSCLC patients not treated surgically. We found that CRT is superior to definitive RT in elderly patients with stage III NSCLC not treated surgically. We also found that in patients that receive CRT, sequential chemotherapy and RT resulted in improved OS compared to concurrent CRT. Treatment of the elderly with stage III NSCLC should involve a multidisciplinary discussion. All patients not eligible for surgery should first be considered for CRT, with either concurrent or sequential RT. Based on our findings, multi-agent chemotherapy is preferred over single-agent regimens in suitable patients. When multi-agent chemotherapy is not feasible, a single-agent regimen is supported by our results. When chemotherapy is contraindicated or not recommended, then definitive RT alone should be considered.”